{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:53:27Z","timestamp":1788335607417,"version":"build-2803163510"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K08329"],"award-info":[{"award-number":["JP19K08329"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Syndromic forms of craniosynostosis occur as a result of dysregulation of various molecular signaling cascades. In humans, a specific gain-of-function mutation (W566R) in PDGFRB causes a distinctive overgrowth syndrome (OMIM # 616592). Affected individuals exhibit distinctive facial features and craniosynostosis. Using CRISPR\/Cas9 gene editing, we generated a mouse model carrying the same pathogenic variant of PDGFRB. The Pdgfrb+\/W565R mice exhibited craniosynostosis with skull-base malformation: thus, we successfully recapitulated the human disease phenotype. In humans, haploinsufficiency of RUNX2, a critical transcription factor in osteogenesis, results in defects of the skull and clavicles due to insufficient membranous ossification. Such phenotypes have been well reproduced in Runx2+\/\u2212 mice. To delineate the molecular mechanisms underlying the development of Pdgfrb-related craniosynostosis, we crossed the Pdgfrb+\/W565R mice with Runx2+\/\u2212 mice. It is noteworthy that the double- mutant mice, i.e. Pdgfrb+\/W565R \u00a0Runx2+\/\u2212 mice, exhibited near complete restoration of the cranial sutures and skull base. The present observation provides in vivo evidence that overactivation of Pdgfrb signaling leads to craniosynostosis through the effect of Runx2. The phenotypic reversal of the cranial structures suggests that modification of the Pdgfrb-Runx2 signaling cascade might offer a novel therapeutic opportunity for craniosynostosis.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf148","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T12:00:24Z","timestamp":1757592024000},"page":"1856-1864","source":"Crossref","is-referenced-by-count":2,"title":["Haploinsufficiency of\n                    <i>Runx2<\/i>\n                    restores the cranial sutures in a mouse model of\n                    <i>Pdgfrb<\/i>\n                    -related craniosynostosis"],"prefix":"10.1093","volume":"34","author":[{"given":"Eri","family":"Ogawa","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine , 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 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